1. Overview

Summary

Pomalidomide combined with Carfilzomib and Dexamethasone (PCd) for induction and consolidation followed by Pomalidomide combined with Dexamethason vs Pomalidomide maintenance for patients with Multiple Myeloma in progression after prior 1st line treatment with Lenalidomide and Bortezomib.

The European Intergroup Trial of the European Myeloma Network EMN
(EMN11/HO114)

Status

open

Members

Participating groups: HOVON, GIMEMA, CEMSG, CMG, NSMG, GR, TR

Study details

Type of study

Prospective randomized Phase II study

Echelon level

Limited site selection

Type of monitoring for this study

Site evaluation visits

Target number of patients

222

Current number of patients

0

Approved by

central EC NL Erasmus MC
CCMO

central EC BE ZNA
FAGG

Study objectives

Primary objectives
• Evaluate the efficacy defined as PFS of pomalidomide maintenance plus dexamethasone versus pomalidomide maintenance in patients who responded (≥ PR) to the combination of pomalidomide (POM), carfilzomib (CAR) and low dose dexamethasone (LD-DEX) for induction and consolidation.
• Evaluate efficacy of the combination of pomalidomide (POM), carfilzomib (CAR) and low dose dexamethasone (LD-DEX) for induction and consolidation in subjects with relapsed or refractory multiple myeloma (MM) after prior first-line treatment in the EMN02/HO95 trial who are refractory to Lenalidomide and/or Bortezomib. This objective will be investigated in patients who have or have not received a prior autologous transplant.

Secondary objectives
• Evaluate the response rate ( after 8 cycles of PCd) before the start of maintenance.
• Evaluate the safety and tolerability of the combination of pomalidomide, carfilzomib and low dose dexamethasone in subjects with relapsed or refractory multiple myeloma.

Exploratory
• Evaluation of biomarkers, including baseline markers predictive of response to pomalidomide combined with carfilzomib and dexamethasone.
• Evaluate the quality of life

Evaluate the gene expression profiles and SNPs in relation to the treatment outcomes and side-effects

2. Patient eligibility criteria

Inclusion criteria

• Included in EMN02/HO95 trial
• The subject must understand and voluntarily sign an informed consent document prior to any study related assessments/procedures.
• Age ≥ 18 years at the time of signing the informed consent form.
• Able to adhere to the study visit schedule and other protocol requirements.
• Documented diagnosis of multiple myeloma and measurable disease (serum M-protein ≥ 10 g/L or urine M-protein ≥ 200 mg/24 hours or abnormal FLC ratio with involved free light chain (FLC) > 100 mg/L) or proven plasmacytoma by biopsy).
• At least prior anti-myeloma regimen according to the EMN02/HO95 trial and documented progression or refractory multiple myeloma as per the IMWG uniform response criteria (Durie, 2006) during or after the last anti-myeloma regimen. Induction therapy followed by autologous stem cell transplant (AutoSCT) and consolidation/ maintenance will be considered as one regimen.
• Patients who have never achieved a response better than PD after at least 2 cycles of lenalidomide containing therapy or who progressed whilst on treatment.
• Normal renal function with a Creatinine Clearance > 45mL/min according to the Modification of Diet in Renal Disease (MDRD) equation for estimation of Glomerular Filtration Rate (GFR)
• WHO performance status score of 0, 1 or 2.
• Patients must be willing and capable to use adequate contraception during the therapy (all men, all pre-menopausal women).
• Patients must be able to adhere to the requirements of the Pregnancy Prevention Risk Management Plan.
• All subjects must agree to refrain from donating blood while on study drug and for 28 days after discontinuation from this study treatment.
• All subjects must agree not to share medication.